LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer

Oncotarget. 2016 Jun 21;7(25):37812-37824. doi: 10.18632/oncotarget.9336.

Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the mechanisms of most lncRNAs in cancers are largely unknown. Because the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is one of the dysregulated lncRNAs in gastric cancer, this study explored its molecular mechanisms in carcinogenesis. RMRP levels in 792 tissues, plasma and gastric juices from patients with various stages of gastric tumorigenesis were analyzed by quantitative reverse transcription-polymerase chain reaction. Overexpression and RNA interference were used to manipulate RMRP expression by RMRP expression vector and small interfering RNAs, respectively. Its mechanisms were evaluated by flow cytometry, real-time cell analysis, plate colony formation assays, and xenograft models. RMRP levels in tissue, plasma and gastric juices from patients with gastric cancer were significantly different from those from controls. Its levels were significantly associated with Borrmann type and metastasis. Plasma and gastric juice RMRP had higher sensitivity and specificity than commonly used markers (such as carcinoembryonic antigen and carbohydrate antigen 19-9). Knockdown of RMRP significantly inhibited cell proliferation in vitro and in vivo, whereas overexpression of RMRP promoted cell growth. Acting as a miR-206 sponge, RMRP modulated cell cycle by regulating Cyclin D2 expression. RMRP plays a crucial role in gastric cancer occurrence and can be used as a novel biomarker for gastric cancer.

Keywords: biomarker; cell cycle; gastric cancer; gene expression; miRNA sponge.

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • CA-19-9 Antigen / metabolism
  • Carcinogenesis
  • Cell Cycle
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cyclin D2 / metabolism
  • Female
  • Gastric Juice / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Transplantation
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Stomach / pathology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • CCND2 protein, human
  • Cyclin D2
  • MIRN206 microRNA, human
  • MicroRNAs
  • RMRP non-coding RNA, human
  • RNA, Long Noncoding